Treatment of chronic fatigue following acute disease

ABSTRACT

THE ADMINISTRATION INTERNALLY TO MAMMALS OF 1-(BHYDROZYETHYL) - 2 - METHYL - 5 - NITROIMIDAZOLE (METRONIDAZOLE), IN A DOSAGE RANGE FOR ADULT HUMANS OF ABOUT 31 TO 1000 MGS. PER TWENTY-FOUR HOUR PERIOD, IS AN EFFECTIVE THERAPEUTIC TREATMENT FOR CHRONIC FATIGUE WHICH SOMETIMES FOLLOWS ACUTE DISEASE.

United States Patent 3,752,889 TREATMENT OF CHRONIC FATIGUE FOLLOWINGACUTE DISEASE James B. Mercer, 13109 W. 95th St.,

Lenexa, Kans. 66215 No Drawing. Continuation-impart of abandonedapphcation Ser. No. 860,062, Sept. 22, 1969. This application Apr. 13,1972, Ser. No. 243,865

Int. Cl. A61k 27/00 US. Cl. 424273 4 Claims ABSTRACT OF THE DISCLOSUREThe administration internally to mammals of l-(B- hydroxyethyl) 2 methyl5 nitroimidazole (metronidazole), in a dosage range for adult humans ofabout 31 to 1000 mgs. per twenty-four hour period, is an effectivetherapeutic treatment for chronic fatigue which sometimes follows acutedisease.

This application is a continuation-in-part of application S'er. No.860,062, filed Sept. 22, 1969, now abandoned.

The invention herein described relates to a method of treating long-termgeneral functional deterioration evidenced by a chronic fatigue whichoccasionally follows the abatement of acute disease or other physicaltrauma which involved the introduction of a foreign protein into thesystem.

The objects of this invention are: to provide a method forsystematically treating the chronic long-term fatigue which occasionallyfollows the abatement of acute disease; to provide such a method whichmay be accomplished through the convenient oral administration oftablets; to provide such a method that is suitable for intensive therapyas well as long term maintenance and intermittent therapy, and toprovide such a method which is usually well tolerated by the patient.

l(fl-hydroxyethyl) 2 methyl 5 nitroimidazole (metronidazole) is a knownalkylatin-g agent of relatively low toxicity which is thought tointerfere with nucleic acid biosynthesis. It appears that metronidazolecan penetrate all tissues of the body quite readily and its function, inthe treatment of chronic fatigue following acute disease, is believedrelated to the suppression of a longterm abnormal immunologic responseof the system to the introduction of foreign protein. The acute diseasepreceding the chonic symptoms apparently may take a variety of forms,such as, trauma to a particular part of the body, pregnancy, viral orbacterial infection, etc., and the resultant fatigue often appearsassociated with a general deterioration which may be likened toaccelerated aging. The agent is readily absorbable from the humanintestinal tract and may be administered orally as well as by vaginal orrectal inserts when indicated.

Clinical observations upon the administration of metronidazole intreatment of the noted symptoms have demonstrated marked patientimprovement in energy and strength, resistance of the skin to bruises,breathing during physical activity, mental activity, reduction of musclecramps and numbness of limbs, and in the ability to rest and sleepeffectively. Persons receiving the drug sometimes showed response by adistinct warming of the entire body, especially the extremities whichhad theretofore been cold for long periods, even months or years. Anotable increase in strength and endurance to perform tasks requiringphysical labor, many of which would not Patented Aug. 14, 1973 ice havebeen attempted prior to the treatment, was also shown as well as afeeling of well being with less anxiety and greater mental and visualacuity.

A typical intense treatment for an average size adult patient comprises250 mgs. of the agent four times daily for a period of about four weeksand then a reduction to mgs. four times daily for several additionalweeks and thereafter further reduction, depending upon the tolerance ofthe patient and the absence of symptoms.

An ultimate effective long-term maintenance dose was found to be as lowas 31 mgs. per day. The most common effective maintenance dose has beendetermined to be about 125- mgs. per day for a substantial percentage ofthe patients with 250 mgs. per day being indicated for other patients,depending on age, size and physical condition. A reasonable maximumdosage appeared to be about 1000 mgs. per day. A renewal of treatmentappeared effective upon a return of symptoms after treatment wasdiscontinued.

Regarding side elfects, some persons were found to experience nausea butit generally disappeared after a few weeks. In rare instances there wasa slight soreness of the mouth or a white tongue and in such cases adosage reduction is indicated. Some dizziness and dryness of the mouthand vagina were occasionally noted and a few persons complained of a badtaste. Also, moderate leukopenia -was occasionly observed, whichnoramlly returned to normal after dosage reduction or completion of atreatment regimen.

Metronidazole has been tested on animals, particularly dogs. The agentappeared effective in improving in physical strength, agility and mentalalertness in dogs otherwise lethargic, the most effective dosage beingabout three (3) mgs. per pound of body weight.

Metronidazole is believed contraindicated in patients under treatmentwith desulfadram (Antabuse) and in uncompensated hypothyroid patients.Because metronidazole appears to cross the placental barrier and enterthe fetal circulation rapidly and further since its effects on fetaldevelopment are not definitely known, it is also thought to becontraindicated during the first trimester of pregnancy.

The initial neurological signs of metroidazole overdose in humansappeared to be increased pulse rate, difficulty in reading small print,difiiculty in handling small objects and insomnia. Progressively, it isunderstood that tachycardia may occur, and a slightly unstable person,especially, may suffer marked swings in mood. Physical exerciseapparently becomes increasingly fatiguing, and weight loss occursdespite substantial food intake. When the medication is withdrawn, theadverse reaction apparently clears totally in one week.

It is to be understood that, while certain practices of this inventionhave been described herein, it is not to be limited to the specific formand dosages described except insofar as such limitations are included inthe claims.

What is claimed and desired to secure by Letters Patent is:

1. The method of treating humans having chronic fatigue following theabatement of acute disease which comprises the repeated administrationto humans of eflective amounts of a pharmaceutical composition whichcontains, as an active ingredient, l-(fl-hydroxyethyD-Z-methyl-S-nitroimidazole.

2. The method as set forth in claim 1 wherein the dosage range of thecomposition in adult humans is about 31 mgs. to 1000 mgs. pertwenty-four hour period.

3 4 3. The method as set forth in claim 1 wherein said References Citedamounts are reduced following the initial administration. n LOS AngelesN 5 29458-163 (1963), pp.

4. The method as set forth in claim 1 wherein said composition isadministered at a dosage of about 125 mgs. per twenty-four hour period.5 STANLEY J. FRIEDMAN, Primary Examiner

